Project Summary Developmental Core A major challenge to including environmental measures to existing studies is capturing the dynamic nature of the environment, particularly how to capture it retrospectively, yet objectively. This is particularly important for HHEAR since it may include many case control genetic studies that would be cross-sectional if blood or urine were used for exposure assessment. The lack of advanced exposure tools to address exposure timing limits research on critical windows of susceptibility ? life stages when individuals are highly vulnerable to environmental exposures. Prospective birth cohorts may capture these relationships, but are expensive both in time and money. The absence of objective retrospective biomarkers that provide information on both the magnitude and timing of fetal and early childhood exposure to multiple chemicals is a major barrier in environmental epidemiology and to HHEAR. A primary mission of the Developmental Core is to develop, validate and standardize precise, unbiased, retrospective biomarkers of multi-chemical exposures at specific life stages including prenatal life, effectively providing data equivalent to a prospective longitudinal design. A major focus will be retrospective exposure reconstruction biomarkers that objectively measure prenatal and infant environment, which are known to be important for both childhood and adult disease. Our Developmental Core has an established track record of innovation over the past three years in the CHEAR Program. We developed tooth matrix-based biomarkers that leverage dentine growth rings to reconstruct the timing and dose of toxic/nutrient elements and organic chemical exposures in fetal life and infancy. We are also developing biomarkers that improve on the standard methods to assess dry blood spots, hair and the placenta, all of which can potentially reconstruct past exposure at different stages of life. It is now recognized that tissue architecture can provide exposure and biological information on toxicity via chemical spatial distribution. Our Core will apply 2D tissue bio-imaging that quantifies the spatial distribution of both metals and biomolecules within tissue sections, using high-resolution laser-based mass spectrometry combined with multiplexed metal-tagged immunolabelling. We are applying this to cancer studies by mapping solid tumors to include spatial information on environmental exposures in cancer. This is one prominent example of the Core aims to contribute to Precision Environmental Medicine. The Developmental Core will integrate with the Targeted Resource, so that our work can be incorporated as services offered to HHEAR Clients. This will be accomplished through shared personnel, resources and the monthly Steering Committee meetings. Our goal is to bring new biomarkers into the HHEAR network as fully developed, high-throughput platforms. Dr. Manish Arora is the Core Leader, and Deputy Director of the Targeted Lab Resource, roles he also played in Mount Sinai CHEAR Lab Hub.